Rheumatobgy and Rehabilitation, 1978,17, 29
A COMPARISON OF BENORYLATE AND NAPROXEN IN DEGENERATIVE ARTHRITIS BY S. R. MAYHEW Eaton Ford, Huntingdon, Cambridgeshire
a curative treatment is found for chronic rheumatic conditions it is useful to have the continued introduction of new symptomatic therapies since patient response varies enormously and individual needs differ. Comparisons of different drugs are useful as they help to 'place' them in terms of efficacy and tolerance. Until relatively recently there has been a tendency to consider therapeutic trials the preserve of the hospital specialist department. However, many chronic disabling conditions are treated mainly by general practitioners and only a small percentage of their patients ever attend a hospital clinic. If, therefore, a therapeutic trial is carried out in such a clinic inevitably it involves a selected population and the results achieved may not accurately reflect those which will be obtained when treating the whole disease spectrum seen by the general practitioner. We therefore feel that there is a strong case for well conducted general practice drug assessments. We decided to carry out a study in osteoarthritis, a condition seen very frequently by most general practitioners and to compare the efficacy and tolerance of two drugs which are widely used in this condition, benorylate (Benoral : Winthrop) and naproxen (Naprosyn : Syntex). UNTIL
METHOD The study which began mid-1975 was multi-centre and between-patient, involving willing informed adult male and female patients suffering from degenerative arthritis of the synovial joints, either confirmed by radiography or having caused symptoms for at least six months. Patients were excluded on the following grounds: under 18 or over 80 years; less than 50 or more than 110 kg; pregnancy; known hepatic or renal insufficiency; a history of peptic ulceration; hypersensitivity to aspirin; receiving anticoagulant, hydantoin, sulphonamide, corticosteroid or other regular anti-arthritic medication. Each patient was treated for a period of two weeks and received according to a random code either benorylate tablets 4.5 g daily or naproxen tablets 0.5 g daily. The tablets were packed in individual sealed boxes so that the observer was 'blind'. A code Accepted for publication August 1977. 29
Downloaded from http://rheumatology.oxfordjournals.org/ at Karolinska Institutet on July 9, 2015
SUMMARY A single-blind two-week comparison of benorylate and naproxen tablets was carried out in 85 patients with painful osteoarthritis. The degree of discomfort, pain at rest and on movement, joint stiffness and difficulty using affected joints all improved during the study with no significant difference between the treatments. Both patients' and observers' assessment of overall improvement favoured benorylate although the difference was not statistically significant. The majority had disease of weight-bearing joints for which Benoral was significantly more effective. Both drugs were well tolerated.
30
RHEUMATOLOGY AND REHABILITATION VOL. XVH NO. 1
RESULTS Ninety-eight patients entered the trial but 13 were excluded because they did not fulfil the stipulated criteria for entry. The remaining 85 record cards were analysed. There were no significant differences between the groups with regard to distribution of sex, age, weight, length of history, initial severity or previous medication. There was a slightly higher proportion of single joints and weight-bearing joints in the benorylate group, but the difference was not significant. The degree of discomfort, pain at rest and on movement, joint stiffness and difficulty using affected joints all improved during the study with no significant difference or apparent trend between the treatments. The patients' assessment of overall effectiveness on days seven and 14 is shown in Table I. It can be seen that the comparison favoured benorylate although the difference was not statistically significant. The observer's assessment of overall improvement on days seven and 14 is shown in Table II. Comparison of the treatments again favoured benorylate although the difference was not statistically significant. The relationship between site ofjoint involvement and observer assessment of overall improvement showed some interesting differences between the treatments (Table ITJ). The majority of patients had involvement of weight-bearing joints and in this group comparison of treatments favoured benorylate, the difference being statistically significant. A relationship was also shown between overall improvement and analgesic therapy received in the week prior to commencement of the trial (Table IV). Most patients had not received analgesic therapy during the week prior to entry and in these patients comparison of the treatments significantly favoured benorylate. In the small group with prior analgesics there was no significant difference between the treatments. SIDE-EFFECTS Both drugs were extremely well tolerated. Five patients reported side-effects with benorylate and four with naproxen. These were almost entirely mild gastro-intestinal upsets. Only one patient needed to withdraw from the trial, a male aged 65 receiving benorylate who complained of nausea and vomiting.
Downloaded from http://rheumatology.oxfordjournals.org/ at Karolinska Institutet on July 9, 2015
break was provided and the observer asked to note if he found out which treatment the patient was receiving. Patients were instructed not to take other analgesics during the study. Assessments were carried out by the same observer on entry, on day seven and on day 14. The joints involved, overall severity, and previous analgesic therapy were recorded. The patients assessed discomfort, pain at rest and on movement, stiffness and difficulty using affected joints. On the seventh and fourteenth days both patient and observer assessments of overall treatment effectiveness were made. The patient used a scale: 0 = not effective, 1 = mildly effective, 2 = moderately effective, 3 = highly effective. The observer used a similar scale: 0 = poor, 1 = satisfactory, 2 = good, 3 = excellent. The treatment groups were compared statistically using the Mann-Whitney U test, and mean scores (and standard errors) derived from these scales are included to illustrate the treatment differences. Side-effects volunteered in response to the question 'How are the tablets suiting you ?' were recorded.
Excellent 2 3
Benorylate Naproxen
Treatment
Benorylate Naproxen
Benorylate Naproxen
14
Day
7
14 7 4
19 11
12 8
Benorylate Naproxen
7
Highly effective
Treatment
Day Moderately effective
TABLE H
8 6
11 9
Mildly effective
3 4
7
4
Not effective
Poor 7 9 3 6
Satisfactory 16 13 9 11
Good 19 16 23 20
2
—
Not stated
3 1
3 1
Not stated
OBSERVER'S ASSESSMENT OF OVERALL IMPROVEMENT
11 19
14 16
TABLE I PATIENT ASSESSMENT OF EFFECTIVENESSt
Downloaded from http://rheumatology.oxfordjournals.org/ at Karolinska Institutet on July 9, 2015
44 41
44 41
Number of patients
44 41
44 41
Number of patients
1.81 (0.12) 1.54(0.14)
1.36(0.12) 1.32(0.14)
Mean overall improvement (±S.E.)
2.12(0.15) 1.93(0.14)
1.83(0.15) 1.63(0.16)
Mean effectiveness (±S.E.)
1
o
I
I
o
0 1 0 0 9
1 0 0 0 3 6
Benorylate Naproxen
Benorylate Naproxen
Benorylate Naproxen
Non-weight-bearing
Both
Combined 20
7 4
0 0
0 1 23
0 2
7 2
Excellent
4 7
19 12
Good
2
—
Not stated
44 41
0 1
5 10
39 30 .
Total
2
7 4 23 20 9 11
3 6
Benorylate Naproxen
Combined
t Benorylate : naproxen P
A COMPARISON OF BENORYLATE AND NAPROXEN IN DEGENERATIVE ARTHRITIS BY S. R. MAYHEW Eaton Ford, Huntingdon, Cambridgeshire
a curative treatment is found for chronic rheumatic conditions it is useful to have the continued introduction of new symptomatic therapies since patient response varies enormously and individual needs differ. Comparisons of different drugs are useful as they help to 'place' them in terms of efficacy and tolerance. Until relatively recently there has been a tendency to consider therapeutic trials the preserve of the hospital specialist department. However, many chronic disabling conditions are treated mainly by general practitioners and only a small percentage of their patients ever attend a hospital clinic. If, therefore, a therapeutic trial is carried out in such a clinic inevitably it involves a selected population and the results achieved may not accurately reflect those which will be obtained when treating the whole disease spectrum seen by the general practitioner. We therefore feel that there is a strong case for well conducted general practice drug assessments. We decided to carry out a study in osteoarthritis, a condition seen very frequently by most general practitioners and to compare the efficacy and tolerance of two drugs which are widely used in this condition, benorylate (Benoral : Winthrop) and naproxen (Naprosyn : Syntex). UNTIL
METHOD The study which began mid-1975 was multi-centre and between-patient, involving willing informed adult male and female patients suffering from degenerative arthritis of the synovial joints, either confirmed by radiography or having caused symptoms for at least six months. Patients were excluded on the following grounds: under 18 or over 80 years; less than 50 or more than 110 kg; pregnancy; known hepatic or renal insufficiency; a history of peptic ulceration; hypersensitivity to aspirin; receiving anticoagulant, hydantoin, sulphonamide, corticosteroid or other regular anti-arthritic medication. Each patient was treated for a period of two weeks and received according to a random code either benorylate tablets 4.5 g daily or naproxen tablets 0.5 g daily. The tablets were packed in individual sealed boxes so that the observer was 'blind'. A code Accepted for publication August 1977. 29
Downloaded from http://rheumatology.oxfordjournals.org/ at Karolinska Institutet on July 9, 2015
SUMMARY A single-blind two-week comparison of benorylate and naproxen tablets was carried out in 85 patients with painful osteoarthritis. The degree of discomfort, pain at rest and on movement, joint stiffness and difficulty using affected joints all improved during the study with no significant difference between the treatments. Both patients' and observers' assessment of overall improvement favoured benorylate although the difference was not statistically significant. The majority had disease of weight-bearing joints for which Benoral was significantly more effective. Both drugs were well tolerated.
30
RHEUMATOLOGY AND REHABILITATION VOL. XVH NO. 1
RESULTS Ninety-eight patients entered the trial but 13 were excluded because they did not fulfil the stipulated criteria for entry. The remaining 85 record cards were analysed. There were no significant differences between the groups with regard to distribution of sex, age, weight, length of history, initial severity or previous medication. There was a slightly higher proportion of single joints and weight-bearing joints in the benorylate group, but the difference was not significant. The degree of discomfort, pain at rest and on movement, joint stiffness and difficulty using affected joints all improved during the study with no significant difference or apparent trend between the treatments. The patients' assessment of overall effectiveness on days seven and 14 is shown in Table I. It can be seen that the comparison favoured benorylate although the difference was not statistically significant. The observer's assessment of overall improvement on days seven and 14 is shown in Table II. Comparison of the treatments again favoured benorylate although the difference was not statistically significant. The relationship between site ofjoint involvement and observer assessment of overall improvement showed some interesting differences between the treatments (Table ITJ). The majority of patients had involvement of weight-bearing joints and in this group comparison of treatments favoured benorylate, the difference being statistically significant. A relationship was also shown between overall improvement and analgesic therapy received in the week prior to commencement of the trial (Table IV). Most patients had not received analgesic therapy during the week prior to entry and in these patients comparison of the treatments significantly favoured benorylate. In the small group with prior analgesics there was no significant difference between the treatments. SIDE-EFFECTS Both drugs were extremely well tolerated. Five patients reported side-effects with benorylate and four with naproxen. These were almost entirely mild gastro-intestinal upsets. Only one patient needed to withdraw from the trial, a male aged 65 receiving benorylate who complained of nausea and vomiting.
Downloaded from http://rheumatology.oxfordjournals.org/ at Karolinska Institutet on July 9, 2015
break was provided and the observer asked to note if he found out which treatment the patient was receiving. Patients were instructed not to take other analgesics during the study. Assessments were carried out by the same observer on entry, on day seven and on day 14. The joints involved, overall severity, and previous analgesic therapy were recorded. The patients assessed discomfort, pain at rest and on movement, stiffness and difficulty using affected joints. On the seventh and fourteenth days both patient and observer assessments of overall treatment effectiveness were made. The patient used a scale: 0 = not effective, 1 = mildly effective, 2 = moderately effective, 3 = highly effective. The observer used a similar scale: 0 = poor, 1 = satisfactory, 2 = good, 3 = excellent. The treatment groups were compared statistically using the Mann-Whitney U test, and mean scores (and standard errors) derived from these scales are included to illustrate the treatment differences. Side-effects volunteered in response to the question 'How are the tablets suiting you ?' were recorded.
Excellent 2 3
Benorylate Naproxen
Treatment
Benorylate Naproxen
Benorylate Naproxen
14
Day
7
14 7 4
19 11
12 8
Benorylate Naproxen
7
Highly effective
Treatment
Day Moderately effective
TABLE H
8 6
11 9
Mildly effective
3 4
7
4
Not effective
Poor 7 9 3 6
Satisfactory 16 13 9 11
Good 19 16 23 20
2
—
Not stated
3 1
3 1
Not stated
OBSERVER'S ASSESSMENT OF OVERALL IMPROVEMENT
11 19
14 16
TABLE I PATIENT ASSESSMENT OF EFFECTIVENESSt
Downloaded from http://rheumatology.oxfordjournals.org/ at Karolinska Institutet on July 9, 2015
44 41
44 41
Number of patients
44 41
44 41
Number of patients
1.81 (0.12) 1.54(0.14)
1.36(0.12) 1.32(0.14)
Mean overall improvement (±S.E.)
2.12(0.15) 1.93(0.14)
1.83(0.15) 1.63(0.16)
Mean effectiveness (±S.E.)
1
o
I
I
o
0 1 0 0 9
1 0 0 0 3 6
Benorylate Naproxen
Benorylate Naproxen
Benorylate Naproxen
Non-weight-bearing
Both
Combined 20
7 4
0 0
0 1 23
0 2
7 2
Excellent
4 7
19 12
Good
2
—
Not stated
44 41
0 1
5 10
39 30 .
Total
2
7 4 23 20 9 11
3 6
Benorylate Naproxen
Combined
t Benorylate : naproxen P
